tbuckley/cabot-search huggingface dataset:
Geographic distribution of clinical trials for common advanced-stage cancers in the United States.
Authors: Wade T. Swenson, Emily Westergard, Zachary Schroeder, Abigail P. Swenson
Journal: Journal of Clinical Oncology (2023)

e18503 Background: This study examines the geographic distribution of clinical trials for common types of metastatic cancer in the United States and the accessibility of these trials to the general population. Methods: We accessed the ClinicalTrials.gov website and conducted a search for interventional clinical trials that were actively recruiting patients for diagnoses of metastatic lung, colon, pancreas, breast, and prostate cancers on November 25, 2022. We identified unique zip codes for all the clinical trials offered and calculated the U.S. population living within 50 miles of a clinical trial site using geographic information system software based on 2020 census data. We created maps for each cancer type, demonstrating the geographic distribution of clinical trial access in the United States. Results: We found a significant number of clinical trials providing access for most Americans diagnosed with the most common types of metastatic cancer. The majority of the United States population lives within 50 miles of a clinical trial. The access varied by cancer type studied, from 75.0% of the United States population for metastatic colon cancer to 90.2% for metastatic lung and breast cancers. See table for details. Conclusions: When considering the accessibility of these trials, we found that a large proportion of the United States population lived within 50 miles of a clinical trial site. This suggests that while many clinical trials are available, they may not be evenly distributed across the country and may not be accessible to all individuals. [Table: see text]
Luveltamab tazevibulin (STRO-002), an anti-folate receptor alpha (FolRα) antibody drug conjugate (ADC), safety and efficacy in a broad distribution of FolRα expression in patients with recurrent epithelial ovarian cancer (OC): Update of STRO-002-GM1 phase 1 dose expansion cohort.
Authors: Ana Oaknin, Lorena Fariñas-Madrid, Carmen García-Duran, Lainie P. Martin, David M. O'Malley, Russell J. Schilder, Denise Uyar, John William Moroney, John Paul Diaz, Alexander I. Spira, Jesus Garcia-Donas, Michael Palumbo, Hatem Dokainish, Lin Liu, Craig Jerome Berman, R. Wendel Naumann
Journal: Journal of Clinical Oncology (2023)

5508 Background: Luveltamab tazevibulin (luvelta) is a novel FolRα-targeting ADC with a stable cleavable linker and a 3-aminophenyl hemiasterlin warhead (DAR of 4) that induces cytotoxic and immunologic cell death. Using site-specific conjugation technology, luvelta is designed to target a broad range of FolRα expressing OC. STRO-002-GM1 is a global phase 1 study evaluating luvelta in patients with relapsed OC. We provide updated data from the initial ovarian expansion cohort. Methods: The study enrolled advanced OC pts who had progressive platinum resistant (PROC) after 1-3 prior lines or platinum sensitive disease after 2-3 prior lines of platinum chemotherapy. Pts were randomized 1:1 to received luveltamab at 4.3 or 5.2 mg/kg given IV every 3 weeks until disease progression. Prophylactic corticosteroid eyedrops were not required/administered. FolRα expression was not required for study entry but was analyzed retrospectively in archival tissue using the FOLR1 IHC assay (Ventana Medical Systems). The scoring paradigm assessed percentage of cells with any intensity expression (TPS). TPS &gt;25% was selected for further analysis. Results: 44 pts were enrolled (23 pts at 4.3 mg/kg and 21 pts at 5.2 mg/kg). For pts with a TPS &gt;25% (n=35), the median prior lines of therapy was 2.5 (range 1-3), 69% had prior bevacizumab treatment, and 83% prior PARP inhibitor treatment. Investigator assessed efficacy data for pts with a TPS &gt;25% are presented in the table. The most common grade ≥ 3 treatment emergent adverse events (TEAEs) included neutropenia (70.5%), arthralgia (18.2%), and anemia (13.6%). G3/4 neutropenia had a higher incidence at 5.2 mg/kg than 4.3 mg/kg (76% vs 65%); most notable for G4 neutropenia (52% vs 22%). 1 pt at each dose level had febrile neutropenia. TEAEs led to dose delay in 80% of pts with a higher incidence at 5.2 mg/kg (95% vs. 65%). TEAEs led to dose reduction in 61% of pts with a higher incidence at 5.2 mg/kg (76% vs. 48%). 1 pt had a G5 sepsis with G4 neutropenia. Neutropenia, arthralgia and anemia were managed with standard medical treatment and dose reductions. Conclusions: These dose expansion data confirm activity of luvelta at starting doses ranging from 4.3-5.2 mg/kg in recurrent OC with FolRα expression as low as TPS&gt;25% and supports further clinical study in this population. The global phase 2/3 REFRaME registration study will evaluate luvelta in PROC pts with TPS &gt;25%. Clinical trial information: NCT03748186 . [Table: see text]
Prevalence of next generation sequencing testing and targetable mutations in cholangiocarcinoma.
Authors: Anuj Shah, Patricia Denise Jones
Journal: Journal of Clinical Oncology (2023)

e16194 Background: Cholangiocarcinoma (CCA) is an aggressive cancer with a poor prognosis. However, next-generation sequencing (NGS) of tumors and new mutation-targeted therapies have the potential to greatly improve treatment outcomes while reducing the systemic toxicities of traditional chemotherapy. In this study, we examined clinical characteristics, treatment outcomes and the use of NGS profiling in a diverse South Florida population of CCA patients to identify mutations as potential therapeutic targets. Methods: We included patients treated at Jackson and University of Miami Health Systems who were diagnosed with CCA between 2018 and 2021. Clinical and demographic characteristics were obtained through retrospective chart review and entered into a REDCap database. We analyzed the association between clinical characteristics, treatment outcomes, use of NGS and race/ethnicity using Pearson’s Chi-square and Kruskal Wallis tests. Results: The majority of our sample, n = 140, had intrahepatic CCA (iCCA), n = 97, followed by extrahepatic CCA (eCCA), n = 27, and perihilar CCA (pCCA), n = 16. Stage, based on AJCC 8 th edition, was most advanced in iCCA and pCCA; 56% had stage III or higher, compared to only 26.2% of eCCA patients. In addition, the median size of the largest iCCA tumor, 7 cm, was significantly larger than that of pCCA, 2.4 cm, and eCCA, 2.2 cm, p = 0.001. NGS was performed in significantly more iCCA cases, 72.2%, compared to pCCA, 37.5%, and eCCA, 59.3%, p = 0.04. TP53 mutations were most common across all CCA subtypes. Other common mutations included CDKN2A, CDKN2B, ERBB2, KRAS, FGFR2, IDH1, and ARID1A, of which only IDH1 and FGFR2 are targetable mutations. There were no significant differences across CCA subtypes in receipt of targeted therapy; overall, 17.1% of patients received targeted therapy. There were no racial differences in stage at presentation or survival in any CCA subtype. While there were numerical differences in the proportion of patients receiving targeted therapy (13.6% of Black, 12.8% of White, and 21.3% of Hispanic), these differences were not statistically significant. Conclusions: There are significant differences in the presentation of CCA subtypes. Examination of NGS results in a larger sample of CCA patients will help expand knowledge on CCA’s mutational profile and permit examination of potential racial disparities in survival or rates of NGS. This work also highlights the need for further targeted therapies against other common mutations in CCA. [Table: see text]
A study of prospective monitoring of patients with recurrent prostate cancer using serial PSMA imaging (18F-DCFPyL).
Authors: Mohammad O. Atiq, Liza Lindenberg, Esther Mena Gonzalez, Baris Turkbey, Fatima Karzai, Megan Hausler, Lisa M. Cordes, Monique Williams, Amy Hankin, James L. Gulley, William Douglas Figg, Peter L. Choyke, Ravi Amrit Madan
Journal: Journal of Clinical Oncology (2023)

TPS5101 Background: 18F-DCFPyL PSMA PET imaging is now FDA approved for patients with high-risk prostate cancer and those with biochemically recurrent prostate cancer (BCR). BCR has been traditionally defined as a rising PSA after definitive surgery and/or radiation have not been curative in patients without tumor findings on a CT or Tc99 bone scan. There are an estimated 25,000-50,000 new cases of BCR in the US annually. BCR patients are usually managed conservatively, often with surveillance since there is no data demonstrating interventions improve survival. Although 18F-DCFPyL will be able to detect disease at the micrometastatic/subclinical level, there is limited prospective data on how these patients should be managed. While great enthusiasm exists to utilize radiation or ADT-based regimens extrapolated from a more advanced disease state, the natural history of subclinical disease seen on 18F-DCFPyL remains unclear (Madan RA et al. J Clin Oncol 2022). Methods: The primary objective of this study is to monitor patients with recurrent prostate cancer to learn about the natural history of 18F-DCFPyL PET positive disease in this patient population. Eligible patients include those who have had prior definitive surgery or radiation, current PSA ≥0.50 ng/mL, testosterone &gt; 100 ng/mL, no evidence of soft tissue disease on CT scan/MRI and no bone lesions on bone scan. Patients will undergo initial imaging with 18F-DCFPyL scans. Those with negative findings on the initial scan will have annual repeat 18F-DCFPyL scans. Patients with positive initial scans will be scanned every 6 months. All patients will have PSA testing every 3 months and will undergo annual CT and Tc99 bone scans. Up to 250 patients will be followed for 5 years or until off-study criteria is met (including new findings on CT/bone scans consistent with metastatic disease or continuous systemic prostate cancer therapy for more than 6 months). In addition to monitoring the imaging changes, we will evaluate patterns of progression on 18F-DCPyL scans over time, analyze PSA doubling time in context of 18F-DCFPyL changes and evaluate circulating biomarkers. ClinicalTrials.gov Identifier: NCT05588128. Clinical trial information: NCT05588128 .
The SPEARHEAD-1 trial of afamitresgene autoleucel (afami-cel [formerly ADP-A2M4]): Pooled analysis of cytokine release syndrome across cohorts in patients with advanced synovial sarcoma.
Authors: Sandra P. D'Angelo, Kristen N. Ganjoo, Jean-Yves Blay, Claudia Valverde, Dejka M. Araujo, Albiruni Ryan Abdul Razak, Axel Le Cesne, Scott Schuetze, Michael J Wagner, Steven Attia, Edouard Forcade, Mihaela Druta, Seth Pollack, Jane Bai, Colin Lunt, Amy Sun, Murray Yule, Cheryl McAlpine, Dennis Williams, Brian Andrew Van Tine
Journal: Journal of Clinical Oncology (2023)

e14531 Background: Afami-cel is an autologous, T-cell receptor T-cell therapy engineered to target melanoma-associated antigen A4 (MAGE-A4) in human leukocyte antigen (HLA) A*02–eligible patients (pts) with advanced solid tumors. SPEARHEAD-1 (NCT04044768) is a Phase 2, two cohort, open-label trial to evaluate the efficacy and safety of afami-cel in pretreated pts with advanced/metastatic synovial sarcoma or myxoid/round cell liposarcoma. Here we report data on cytokine release syndrome (CRS) in the pts with advanced synovial sarcoma treated with afami-cel across Cohort 1 and Cohort 2. Methods: Eligible pts had advanced synovial sarcoma and were HLA-A*02 positive with MAGE-A4–positive tumors. Pts received afami-cel after lymphodepleting chemotherapy containing fludarabine and cyclophosphamide. Tocilizumab administration was permitted for Grade 1 CRS if symptoms persisted for ≥ 24 hours or if the pt had co-morbidities, and for Grade ≥2 CRS. Results: As of August 29, 2022, 72 pts with synovial sarcoma received afami-cel (n = 44 Cohort 1; n = 28 Cohort 2). Afami-cel dose range was 1.92–10.00×10 9 transduced T-cells. The median age was 39.5 years (range: 16–73 years), 47.2% of pts were female, 88.3% of pts were white, and tumor MAGE-A4 expression H-score was 244.5 (range: 66–300). CRS occurred in 72.2% of the pts with synovial sarcoma receiving afami-cel, including Grade 1 in 50% (36/72), Grade 2 in 20.8% (15/72), and Grade 3 in 1.4% (1/72) of pts as per American Society for Transplantation and Cellular Therapy grading. The median time to onset was 2.5 days (range: 1–5 days), and the median time to resolution was 3 days (range: 1 to 14 days). Twenty-seven of 72 (37.5%) pts received at least one dose of tocilizumab. Consistent with expectations, higher serum IL-6 levels were associated with CRS events and the indicated use of tocilizumab for management. RECIST v1.1 responses were observed in pts with and without CRS. Correlation of clinical factors and CRS with response will be presented. Conclusions: CRS was common after afami-cel administration but was mostly low grade. Administration of tocilizumab in SPEARHEAD-1 was effective in the management of CRS. Clinical trial information: NCT04044768 .
Clinical characterization of MYC family proto-oncogene amplification in solid tumors from Chinese patients.
Authors: Zhiliang Liu, Tiantian Han, Rongrong Kong, Didi Guo, Mengjuan Wang, Yuwei Dong, Siqi Chen, Jiawen Fan, Wanglong Deng, Ran Ding, Fanfeng Bu
Journal: Journal of Clinical Oncology (2023)

e15140 Background: The dysregulation of the MYC family oncogenes ( c-MYC, MYCN and MYCL) play critical roles in tumorigenesis, prognosis and immune escape. MYC inactivation can result in sustained tumour regression and many therapeutic agents that directly target MYC are under development. MYC signaling is associated with tumor cell PD-L1, overall immune cell infiltration. Herein, we explore MYC family proto-oncogene amplification profiles and clinical characterization in chinese solid tumors. Methods: This research comprehensively characterized gene mutations by next-generation sequencing (NGS) in 23990 chinese solid tumors tissues to reveal the prevalence of MYC family proto-oncogene amplification(MYC AMP) and the association with Tumor mutational burden(TMB) and microsatellite instability(MSI). Results: The prevalence of MYC AMP (copy number, CN≥5) in the cohort was 2.1% (504/23,990), in which ovarian cancer (7.6%, 22/289) showed the highest prevalence, followed by breast cancer (6.1%, 26/429), esophagus cancer (5.9%, 17/287). Only one glioma patient(pt) carried co-amplification of MYCN and c-MYC. In 504 MYC AMP pts, c-MYC AMP accounted for 93.7%(472/504), MYCN and MYCL AMP accounted for 6.5%(33/504) in total. The CN was significantly higher in MYCN and MYCL AMP pts than c-MYC AMP pts (22.9 vs 7.6, p &lt; 0.0001). MSI-H showed a lower detection rate in MYC AMP pts other than Non-MYC AMP pts (0% vs 1.2%, p &lt; 0.05). The proportion of TMB-L in MYC AMP pts was similar to Non-MYC AMP pts (90.9% vs. 90.1%, p &gt; 0.05). Conclusions: In totally, 2.1% of chinese solid tumor pts had MYC high level AMP, mainly c-MYC Amp. The CN was higer in MYCN/ MYCL AMP pts than c-MYC AMP pts. In addition, MYC AMP pts tended to have MSS and TMB-L, suggesting that MYC may be a novel target for tumor immunotherapy. MYC inhibitor combines with immunotherapy may be an important direction for the treatment of MYC AMP pts.
Prevalence and characteristics analysis of CDKN2A/B deletion in glioma.
Authors: Dongxiao Zhuang, Tiantian Han, Didi Guo, Rongrong Kong, Siqi Chen, Yuwei Dong, Mengjuan Wang, Ran Ding, Wanglong Deng, Fanfeng Bu
Journal: Journal of Clinical Oncology (2023)

e14026 Background: Glioma is the most common type of brain malignancy in adults. The 5th edition of the World Health Organization (WHO) highlighted the homozygous deletion of the CDKN2A/2B as a clinically important molecular alteration in IDH-mutant glioma. In the study, we reported the prevalence and characteristics analysis of CDKN2A/B deletion in glioma. Methods: This study retrospectively analyzed the genomic alteration of 2390 Chinese glioma patients during 2019-2022. Next-generation sequencing (NGS) of 131-gene profiling was performed to detect gene mutations in tumors of the patients. Patients were divided into two groups for copy number (CN) variation set, as heterozygous deletion (CN&gt; 0.5, HET-del) or homozygous deletion (CN≤ 0.5, HOM-del) group. Results: A total of 743 (31%) cases were detected with CDKN2A/B deletion, 21 cases were children (&lt; 18 years old), and 722 cases were adults, with a mean age of 53 years (0-85 years). CDKN2A/B deletion showed a higher frequency in the subgroup of IDH-wildtype glioma compared with IDH-mutant glioma in adults (39% vs. 15%, p&lt;0.005). The age showed no significant difference between CDKN2A/B HET-del (n=420) and HOM-del (n=323) patients (average age: 53, p = 0.74). In both of the two groups, the most frequently somatic mutated genes were TERT, EGFR, PTEN. However, NF1 mutations were significantly enriched in the HET-del group (21% vs. 12%，p&lt;0.005). Conclusions: Taken together, CDKN2A/B deletion were found in 31% glioma patients and showed higher frequency in IDH-wildtype glioma. NF1 mutations were significantly enriched in the HET-del group, which may reveal distinct prognosis and pathogenic mechanisms in glioma.
Efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy in patients with high-risk UTUC.
Authors: Yuanjie Niu, Hong Zheng Li, Hailong Hu, Zesheng An, Chong Shen, Zhouliang Wu, Yunkai Qie, Yiduo Bai, Gangjian Zhao, Houyuan Chen, Shizheng Guo
Journal: Journal of Clinical Oncology (2023)

e16609 Background: Urothelial carcinomas (UCs) are the sixth most common tumor. Among them, UTUCs are uncommon, accounting for only 5-10% of UCs. Currently, radical nephroureterectomy (RNU) remains the gold standard of treatment for UTUC. Neoadjuvant chemotherapy treatment can be used for specific UTUC patients, especially for highly staged and/or grade tumors, such as kidneys with potentially decreased renal function after RNU. Neoadjuvant therapy is a series of treatments administered preoperatively for UTUC, mainly chemotherapy, and in recent years, novel therapies of immunotherapy have emerged. Since conventional cisplatin neoadjuvant regimens also require high preoperative renal function, neoadjuvant chemotherapy regimens such as immunotherapy provide more effective and feasible treatments for patients who are intolerant to current cisplatin chemotherapy regimens. However, there is a lack of valuable studies worldwide on novel regimens such as immunotherapy for UTUC. The aim of this study was to explore a novel preoperative neoadjuvant regimen of immunotherapy combined with chemotherapy for UTUC. To further observe the feasibility and effectiveness of this regimen in the field. Methods: 9 high-risk UTUC patients were included in this study. Among them, 7 had unilateral ureteral tumors. 1 had a unilateral renal pelvic tumor. 1 had unilateral pelvic ureteral tumor. Among them, 2 were combined with bladder tumor. All patients were given 3 cycles of tislelizumab 200 mg combined with albumin paclitaxel 200 mg after a thorough evaluation. The treatment cycles were 21 days. Imaging evaluation and surgical resection were given within 15-20 days after the end of the last treatment cycle. Results: 3 patients underwent radical nephroureterectomy with postoperative pathology suggesting SD status of the tumor. 1 patient underwent ureteral reimplantation with tumor-negative postoperative pathology (cCR) and 2 patients underwent ureteroscopic biopsy, 1 of whom had tumor-negative pathology (cCR). 2 patients declined surgical treatment with RNU, one patient had imaging confirmation that the tumor was in SD, and the other showed no evidence of tumor presence on imaging and cytology (cCR). 1 patient was treated intermittently for grade 2 myocardial adverse effects (the remaining patients had adverse effects mostly limited to grade 1, with alopecia and malaise as common symptoms). Conclusions: The characteristics of epithelial carcinoma of the upper urinary tract have led to a reduced intention of some patients to undergo RNU treatment after the completion of NAC treatment. Although the present study failed to obtain ideal pathological information after RNU, the clinical treatment effect (cCR 30%) presented in combination with imaging and cytological results reveals to some extent the promising prospect of future UTUC patients treated with NAC.
Components of total cost of care in real-world patients with mPDAC who received first-line FOLFIRINOX or Gem/Abrax.
Authors: Jared Hirsch, Paul Cockrum, Samantha Tomicki, Gabriela Dieguez, Prachi Bhatt, George P. Kim
Journal: Journal of Clinical Oncology (2023)

e16282 Background: FOLFIRINOX (FFX) and Gemcitabine/Abraxane (Gem/Abrax) are two recommended options for the treatment of metastatic pancreatic ductal adenocarcinoma (mPDAC). There is limited research assessing differences in costs between real-world patients with mPDAC who received first-line (1L) FFX or Gem/Abrax. Methods: We used ICD-10 diagnosis codes to identify patients aged 65+ with mPDAC without end-stage renal disease in the 2018-2021 Medicare Parts A, B, and D 100% Research Identifiable Files (RIF) data. Total cost of care (TCOC) represents mean Medicare paid amounts and patient cost sharing. Lines of therapy (LOTs) were assigned based on therapies used. LOTs ended the day before a new chemotherapy began, 28 days after the last chemotherapy (if no new chemotherapy), or upon death. Study patients were treated with FFX or Gem/Abrax as a 1L therapy. Results: We identified 8,889 patients with mPDAC that received an 1L FFX regimen between 2018 and 2021 and 15,053 patients that received a Gem/Abrax regimen in the same period. Total cost of care was similar among the two cohorts ($7,187 per administration cycle among patients receiving FFX vs. $7,240 among those receiving Gem/Abrax in 1L). Patients receiving Gem/Abrax had higher chemotherapy costs ($2,980) than FFX ($406), however, patients receiving FFX had higher granulocyte colony-stimulating growth factor costs ($1,592 FFX vs. $293 Gem/Abrax) and higher Other Part B costs ($1,301 FFX vs. $876 Gem/Abrax). Inpatient costs were similar between FFX ($1,732) and Gem/Abrax ($1,615), while outpatient costs were higher for patients receiving FFX ($1,549) than patients receiving Gem/Abrax ($847). Conclusions: Among Medicare Fee-For-Service patients with mPDAC, patients receiving FOLFIRINOX (FFX) or Gemcitabine/Abraxane (Gem/Abrax) as a first-line therapy incurred similar costs of care overall, with different distributions across service categories. While therapy costs were lower among patients receiving generic FFX than those receiving branded Gem/Abrax, higher costs from supportive therapies offset those differences.